Bispecific antibodies that bind to CD38 and CD3

Abstract

The invention provides novel heterodimeric proteins including heterodimeric antibodies.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application is a continuation of U.S. patent application Ser. No. 14 / 673,695 filed Mar. 30, 2015, which in turn claims priority under 35 U.S.C. § 119 to U.S. Provisional Patent Applications Nos. 61 / 972,172, filed Mar. 28, 2014, 62 / 025,974, filed Jul. 7, 2014, and 62 / 025,931, filed Jul. 17, 2014, the entire contents of which are incorporated herein for all purposes by this reference and specifically for the figures, legends and data outlined herein.INCORPORATION BY REFERENCE OF A SEQUENCE LISTING SUBMITTED AS A TEXT FILE VIA EFS-WEB[0002]This application contains, as a separate part of disclosure, a Sequence Listing in computer-readable form (filename: 50362A_Seqlisting.txt; Size: 934,047 bytes; created Jan. 22, 2020), which is incorporated by reference in its entirety.TECHNICAL FIELD[0003]The present invention describes novel immunoglobulin compositions that simultaneously co-engage antigens, where both of the antigens are bound mono...

AI Technical Summary

Benefits of technology

The present invention provides heterodimeric antibodies that bind to CD3 and CD38. These antibodies have a first heavy chain and a second heavy chain that each have a variable Fc domain and a single chain Fv region (scFv) that bind to CD3. The scFv has a specific sequence. The antibodies also have a first light chain and a second light chain that each have a variable light domain (VL) that bind to CD3. The scFv has a specific sequence. The antibodies can be used to treat CD3 and CD38-related diseases.

Problems solved by technology

While these formats can be expressed at high levels in bacteria and may have favorable penetration benefits due to their small size, they clear rapidly in vivo and can present manufacturing obstacles related to their production and stability.

A principal cause of these drawbacks is that antibody fragments typically lack the constant region of the antibody with its associated functional properties, including larger size, high stability, and binding to various Fc receptors and ligands that maintain long half-life in serum (i.e., the neonatal Fc receptor FcRn) or serve as binding sites for purification (i.e., protein A and protein G).

One significant drawback of these formats is that, because they build new antigen binding sites on top of the homodimeric constant chains, binding to the new antigen is always bivalent.

In spite of the recent progress in the discovery and development of anti-cancer agents, many forms of cancer involving CD38-expressing tumors still have a poor prognosis.

Thus while bispecifics generated from antibody fragments suffer biophysical and pharmacokinetic hurdles, a drawback of those built with full length antibody-like formats is that they engage co-target antigens multivalently in the absence of the primary target antigen, leading to nonspecific activation and potentially toxicity.

Images